Mitochondrial ferritin explained

Mitochondrial ferritin is a ferroxidase enzyme that in humans is encoded by the FTMT gene.^[1]

It is classified as a metal-binding protein which is located within the mitochondria. After the protein is taken up by the mitochondria it can be processed into a mature protein and assemble functional ferritin shells.

Structure

Its structure was determined at 1.70 Å through the use of X-ray diffraction and contains 182 residues. It is 67% helical. The Ramachandran plot shows that the structure of mitochondrial ferritin is mainly alpha helical with a low prevalence of beta sheets.

Further reading

• Langlois d'Estaintot B, Santambrogio P, Granier T, etal . Crystal structure and biochemical properties of the human mitochondrial ferritin and its mutant Ser144Ala. . J. Mol. Biol. . 340 . 2 . 277–93 . 2004 . 15201052 . 10.1016/j.jmb.2004.04.036 .
• Zanella I, Derosas M, Corrado M, etal . The effects of frataxin silencing in HeLa cells are rescued by the expression of human mitochondrial ferritin. . Biochim. Biophys. Acta . 1782 . 2 . 90–8 . 2008 . 18160053 . 10.1016/j.bbadis.2007.11.006 .
• Wilkinson J, Di X, Schönig K, etal . Tissue-specific expression of ferritin H regulates cellular iron homoeostasis in vivo. . Biochem. J. . 395 . 3 . 501–7 . 2006 . 16448386 . 1462685 . 10.1042/BJ20060063 .
• Iwasaki K, Mackenzie EL, Hailemariam K, etal . Hemin-mediated regulation of an antioxidant-responsive element of the human ferritin H gene and role of Ref-1 during erythroid differentiation of K562 cells. . Mol. Cell. Biol. . 26 . 7 . 2845–56 . 2006 . 16537925 . 1430308 . 10.1128/MCB.26.7.2845-2856.2006 .
• Hasan MR, Tosha T, Theil EC . Ferritin contains less iron (59Fe) in cells when the protein pores are unfolded by mutation. . J. Biol. Chem. . 283 . 46 . 31394–400 . 2008 . 18805796 . 2581568 . 10.1074/jbc.M806025200 . free .
• Cazzola M, Invernizzi R, Bergamaschi G, etal . Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia. . Blood . 101 . 5 . 1996–2000 . 2003 . 12406866 . 10.1182/blood-2002-07-2006 . 5729203 . free .
• Faniello MC, Fregola A, Nisticò A, etal . Detection and functional analysis of an SNP in the promoter of the human ferritin H gene that modulates the gene expression. . Gene . 377 . 1–5 . 2006 . 16797877 . 10.1016/j.gene.2006.02.034 .
• Iwasaki K, Hailemariam K, Tsuji Y . PIAS3 interacts with ATF1 and regulates the human ferritin H gene through an antioxidant-responsive element. . J. Biol. Chem. . 282 . 31 . 22335–43 . 2007 . 17565989 . 2409283 . 10.1074/jbc.M701477200 . free .
• MacKenzie EL, Tsuji Y . Elevated intracellular calcium increases ferritin H expression through an NFAT-independent post-transcriptional mechanism involving mRNA stabilization. . Biochem. J. . 411 . 1 . 107–13 . 2008 . 18076382 . 2702759 . 10.1042/BJ20071544 .
• Drysdale J, Arosio P, Invernizzi R, etal . Mitochondrial ferritin: a new player in iron metabolism. . Blood Cells Mol. Dis. . 29 . 3 . 376–83 . 2002. 12547228 . 10.1006/bcmd.2002.0577 .
• Fisher J, Devraj K, Ingram J, etal . Ferritin: a novel mechanism for delivery of iron to the brain and other organs. . Am. J. Physiol., Cell Physiol. . 293 . 2 . C641–9 . 2007 . 17459943 . 10.1152/ajpcell.00599.2006 . 2673703 .
• Campanella A, Rovelli E, Santambrogio P, etal . Mitochondrial ferritin limits oxidative damage regulating mitochondrial iron availability: hypothesis for a protective role in Friedreich ataxia. . Hum. Mol. Genet. . 18 . 1 . 1–11 . 2009 . 18815198 . 10.1093/hmg/ddn308 . 3298861.
• Bou-Abdallah F, Biasiotto G, Arosio P, Chasteen ND . The putative "nucleation site" in human H-chain ferritin is not required for mineralization of the iron core. . Biochemistry . 43 . 14 . 4332–7 . 2004 . 15065877 . 10.1021/bi0498813 .
• Binning RC, Bacelo DE . Computational modeling of the dizinc-ferroxidase complex of human H ferritin: direct comparison of the density functional theory calculated and experimental structures. . J. Biol. Inorg. Chem. . 14 . 8 . 1199–208 . 2009 . 19585161 . 10.1007/s00775-009-0563-z . 23855417 .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 528928 . 10.1101/gr.2596504 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . free .
• MacKenzie EL, Ray PD, Tsuji Y . Role and regulation of ferritin H in rotenone-mediated mitochondrial oxidative stress. . Free Radic. Biol. Med. . 44 . 9 . 1762–71 . 2008 . 18325346 . 2682214 . 10.1016/j.freeradbiomed.2008.01.031 .
• Bou-Abdallah F, Santambrogio P, Levi S, etal . Unique iron binding and oxidation properties of human mitochondrial ferritin: a comparative analysis with Human H-chain ferritin. . J. Mol. Biol. . 347 . 3 . 543–54 . 2005 . 15755449 . 10.1016/j.jmb.2005.01.007 .
• Faniello MC, Di Sanzo M, Quaresima B, etal . p53-mediated downregulation of H ferritin promoter transcriptional efficiency via NF-Y. . Int. J. Biochem. Cell Biol. . 40 . 10 . 2110–9 . 2008 . 18372207 . 10.1016/j.biocel.2008.02.010 . 10447/35800 . free .
• Snyder AM, Wang X, Patton SM, etal . Mitochondrial ferritin in the substantia nigra in restless legs syndrome. . J. Neuropathol. Exp. Neurol. . 68 . 11 . 1193–9 . 2009 . 19816198 . 3024883 . 10.1097/NEN.0b013e3181bdc44f .

Notes and References

1. Levi S, Corsi B, Bosisio M, Invernizzi R, Volz A, Sanford D, Arosio P, Drysdale J . A human mitochondrial ferritin encoded by an intronless gene . J. Biol. Chem. . 276 . 27 . 24437–40 . July 2001 . 11323407 . 10.1074/jbc.C100141200 . free .